Regulation of EZH2 in Triple-Negative Breast Cancer

Overexpression of the Polycomb group protein EZH2 in estrogen receptor negative (ER-) breast cancer promotes metastasis. EZH2 has been mainly studied as a transcriptional repressor and an enzymatic component of the Polycomb Repressive Complex 2 (PRC2) that trimethylates histone H3 at lysine 27 (H3K27me3). However, how EZH2 drives metastasis, despite the low levels of H3K27me3 observed in ER- breast cancer, and the function of extranuclear EZH2 are unknown. Here, we report that phosphorylation of EZH2 at T367 plays a critical role in breast cancer invasion and metastasis. In human invasive carcinomas and distant metastasis, cytoplasmic EZH2 phosphorylated at T367 is significantly associated with ER- disease and low H3K27me3 levels. We uncover a previously unrecognized PRC2-independent mechanism by which p38-mediated EZH2 phosphorylation at T367 promotes EZH2 cytoplasmic localization and potentiates EZH2 binding to vinculin and other cytoskeletal regulators of cell migration and invasion. Ectopic expression of a phospho-deficient mutant of EZH2, where T367 has been replaced with Ala, is sufficient to inhibit EZH2 cytoplasmic expression, to disrupt binding to cytoskeletal regulators, and to reduce EZH2-mediated adhesion, migration, invasion, and the development of spontaneous metastasis. These results point to a novel non-canonical mechanism for EZH2 pro-metastatic function and suggest a new therapeutic approach for metastatic breast cancer.PHDMolecular & Cellular Path PhDUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/155274/1/tanwar_1.pd

Evaluation of anxiety and depression in chronic liver disease patients.

Objective: To evaluate the risk factors of anxiety and depression in chronic liver disease patientsMethodology: In this longitudinal study seven hundred fifty-five patients (mean age 51+ 5 years, 59% males). All the patients were suffering from chronic hepatitis B, chronic Hepatitis C, Alcoholic liver disease and non-alcoholic fatty stomach disease. Questionnaires were included anxiety, using the Hamilton depressing rating scale (HDRS) and Hamilton anxiety scale (HARS), including socio-demographic, health status and family support. The criteria for inclusion in the study were having liver disease from last 15 months. Clinical functional and psychological assessments were performed.Results: In this study patients with depression was 59.3%, with anxiety 17.4% patients and both anxiety and depression were noted in 36.7% patients. After measuring and calculating all the variables score of depression and anxiety were recorded. A higher HDRS score was noted in patients older than 46 years (p=0.024). Patients with gastrointestinal bleeding had a prominent higher score of anxiety than those without bleeding (p=0.019). A higher HARS score was present in the women (p=0.011), unemployed patients (p=0.009) and those with alcoholic liver disease (p=0.006). There was direct correlation between the duration of disease and the value of HDRA and HARS score.Conclusion: In the chronic liver disease patients’ depression and anxiety are increasingly high with passage of time, gastrointestinal bleeding and unemployment. Increased prevalence of relax by patients are more likely to be due to the low acceptance of disease prognosis

Dynamics of Leverage Policies: Comparative Analysis of Shariah Compliant and non- Compliant Firms

This study aims to check the influence of corporate governance on the leverage policies of Shariah-compliant and NSC firms. Also, their speed of adjustment toward optimal leverage is compared. The dynamic system GMM technique confirms that corporate governance is an essential feature in leveraging the policies of Shariah-compliant and NSC firms. However, the board size, board independence, CEO duality, and auditor reputation determine the leverage policy of Shariah-compliant firms. Board size, ownership concentration, and auditor reputation determine the leverage policy in NSC firms. Additionally, NSC firms adjust their leverage more quickly than Shariah-compliant firms. &nbsp

Is there any benefit of drain placement on postoperative complications in patients undergoing the sistrunk procedure?

Abstract Introduction Same-day, outpatient Sistrunk procedure is commonly performed to manage thyroglossal duct cyst anomalies and may lead to postoperative complications. Surgical drains are placed to prevent complications, but recent observations show no advantage and rather increased health care costs and patient discomfort. Objective The study evaluated if drain placement in the Sistrunk procedure offers any benefit on postoperative complications. Methods A retrospective analysis of patient records having undergone same-day, outpatient Sistrunk procedure from 2004 to 2014 was done. Of 58 (38 male and 20 female) patients included, 38 did not have drains placed and the remaining 20 had drains placed. Mean and median age of patients was 18.1 and 13.5 years, respectively. Postoperative complications of patients with drains versus those without drains were statistically analyzed. Results Overall, about 10% of patients had hematoma/seroma (H-S), with 6.9% of patients needing aspiration for H-S; 3.4% had wound infections; and 1.7% had pus formation. No statistically significant differences in Sistrunk-related complications between patient groups (with drain or without drain) were seen using Fisher exact (two-sided) test: H-S (p = 0.08); need for aspiration (p = 0.29); wound infection (p \u3e 0.05); and pus formation (p = 0.35). Chi-square test also did not show any significant difference in the groups in terms of number of follow-ups. Conclusion Surgical placement of a drain in the Sistrunk procedure does not seem to offer any advantage in terms of reducing common postoperative complications. Same-day Sistrunk procedure without any drain placement may be a safer alternative without necessitating hospitalization. More studies with larger sample size are needed for further substantiatio

Clinical Presentation and Surgical Outcomes of Chronic Subdural Hematoma

Objective: The aim of this study was to access clinical presentation of chronic subdural hematoma and to evaluate the surgical outcome of evacuation of chronic subdural hematoma after single burrhole craniotomy with a close drainage system under local anesthesia. Material & Methods:  A descriptive study conducted in the Neurosurgery Department of Khairpur Medical College Sindh. 30 patients of chronic subdural hematoma were included. Patients prepared for evacuation of chronic subdural hematoma through single burr hole followed by closed drainage system for two days. Results:  The most common feature was gait disturbance followed by Hemiparesis and headache. Coexisting diseases were hypertension, Diabetes mellitus and Chronic Liver Disease, etc. and causes of CSDH were head injury (trivial trauma) and anticoagulant. Surgical decisions were taken on the bases of clinical presentation and radiological findings of patients. Surgical procedure single burrhole craniotomy followed by irrigation with normal saline and close drainage system for two days. On post-operative follow-up, a recurrence of CSDH occurred in two patients. Conclusion:  Single burrhole craniotomy with close drainage system is a simple and safe procedure under local anesthesia for treatment of chronic subdural hematoma. Keywords:  CSDH (chronic subdural hematoma), GCS (Glasgow coma score), Burrhole craniotomy, Neurosurgery & Subdural drain

Frequency of sensorineural hearing loss in chronic suppurative otitis media

Abstract Chronic suppurative otitis media (CSOM) is defined as chronic otorrhea (i.e., lasting \u3e 6-12 weeks) through a perforated tympanic membrane. It is generally associated with some degree of conductive hearing loss. However, recurrent ear infections due to perforated eardrum result in absorption of toxins and macromolecules into the cochlea leading to sensorineural hearing loss (SNHL). We planned to determine the frequency of sensorineural hearing loss in chronic suppurative otitis media. A descriptive cross-sectional study was conducted at Aga Kgan University Hospital, Karachi, from October 2013 to March 2014. Average threshold of speech frequencies was calculated via pure tone audiogram for both diseased and normal contralateral ear. A mean of \u3e25db in diseased ear was labelled as positive case for SNHL. SNHL was reported in 64(52%) patients and the frequency was found to increase with increasing duration. Patients with CSOM should be counselled regarding the risk of developing SNHL if left untreated

Attitudes, techniques and trends in endodontic treatment by the house surgeons in dental institutes - Karachi

Background: The attitudes, techniques and different approaches toward endodontic treatment reflects the quality of the root canal treatment (RCT) performed by general dental practitioners. Endodontic therapy has been associated with the pre-operative diagnosis of the tooth, microbial factors, quality of RCT. Environmental factors in which the dentist works may also impact quality of RCT. Materials and Methods: The present cross-sectional study was conducted in October 2013 to evaluate the attitudes, techniques and trends in endodontic treatment procedures amongst the house surgeons in dental institutes of Karachi. A cluster sampling technique was employed, and 170 structured questionnaires were distributed to all registered house surgeons employed in six different dental institutes of Karachi. All returned forms were evaluated by a single operator. Descriptive statistics and frequency distribution was analyzed using SPSS version 19. Results: From all given questionnaires, 150 filled questionnaires were collected from participants, which is 88.23% response rate. Conclusion: It was concluded that the recently graduated dental practitioners lacked expertise in certain regards. They were performing procedures that are deviated from the well acknowledged endodontic quality guidelines

Comparison of Frequency of Recurrence after Burr Hole Evacuation of Chronic Subdural Hematoma with or without Subdural Drain.

Chronic subdural hematoma (CSDH) is known to have a significant recurrence rate. The rate of recurrence of chronic subdural hematoma after surgery ranges from roughly 5% to 30%.  Burr hole evacuation without drainage is performed as a first line of treatment for CSDH. As there is controversy in literature regarding the use of drainage after burr hole evacuation, the results of my study may be helpful for selecting a proper treatment modality as a first line of treatment for CSDH in terms of recurrence. The objective of this study was to compare the frequency of recurrence after burr hole evacuation of CSDH with and without subdural drain. It was a randomized controlled trial conducted in Department of Neurosurgery, Allied hospital, Faisalabad form Aug 2016 to Aug 2018 RESULTS:In our study, out of 130 cases(65 in each group). 84.62%(n=55) in Group-A and 76.92%(n=50) in Group-B were between above 40 years of age whereas 15.38%(n=10) in Group-A and 23.08%(n=15) were between 18-40 years of age, mean+sd was calculated as  64.03+7.61 years in Group-A and 62.28+7.83 years in Group-B, 78.46%(n=51) in Group-A and 72.31%(n=47) in Group-B were male while 21.54%(n=14) in Group-A and 27.69%(n=18) in Group-B were females, comparison of frequency of recurrence after burr hole evacuation of CSDH with and without subdural drain shows 10.77%(n=7) in Group-A and 27.69%(n=18) in Group-B, p value was 0.01 showing a significant difference. CONCLUSION: We concluded that the frequency of recurrence after burrhole evacuation of CSDH is significantly lower with drain when compared without subdural drain

IN VITRO ANTIBACTERIAL ACTIVITY OF MEDICINAL PLANTS TURMERIC, CHINNAMON, AND CLOVE AGAINST GM (+VE) AND GM (-VE) BACTERIA

Objective: Various diseases are caused by different pathogenic microorganisms. Antibiotics are being used for treatment of these infectious diseases, yet unpredictable utilization of it leads towards antibacterial resistance. It is required to discover better approaches to battle against antibacterial resistance. Therefore, the study aimed to detect antibacterial sensitivity of ethanol extracts of Curcuma longa (turmeric), Cinnamomumzeylanicum (clove) and Syzygiumaromaticum (cinnamon) against Syaphylococcus aureus and E coli. Methods: Prior to sensitivity testing, ethanol oils were extracted by an electric blender and each of the bacteria strains were cultured onto blood agar plate. Antibacterial activity was tested by agar well diffusion method where three different concentrations (50 μl, 75 μl and 100 μl) of selected plants extract were used so far as to measure the inhibition zone. Inhibition zone of the ethanol extract of these plants were calculated where three were found to be sensitive against Syaphylococcus aureus and E coli. Results: Greater inhibition zone 14.5 mm, 18.25 mm, 21.5 mm at100 μl against Syaphylococcus aureus in case of cinnamon whereas the least inhibition zone was showed by turmeric and it was 9.00 mm, 11.00 mm, and 12.75 mm at 100 μl extract against E. coli. Conclusion: Overall, all the ethanol extracts were found to effective against these two bacteria but cinnamon can be used as more effective antibacterial agent in both human and veterinary field after the toxicological test